[성분] 피모벤단 (Pimobendan)

상세 약물 자료

Pharmacology and mechanism of action

Pimobendan is both a positive inotrope and a vasodilator. The vasodilator effects occur via inhibition of Phosphodiesterase III (PDE III). Phosphodiesterase III is the enzyme that degrades cyclic adenosine monophosphate (cAMP); therefore its action is to increase intracellular concentrations of cAMP. There may be some inhibition of PDE V in the pulmonary circulation. The inotropic effects of pimobendan are attributed to its action as a calcium sensitizer rather than the PDE inhibition. By acting as a calcium sensitizer, it increases the interaction of troponin C with contractile proteins and acts as an inotropic agent. The benefits in heart failure are caused by both positive inotropic effects and vasodilating properties. Other beneficial effects may include anti-inflammatory activity, increased sensitivity of baroreceptors, increased lusitropy, and decreased platelet aggregation. The cardiovascular effects occur after 1 hour and persist for 8-12 hours after administration. Pimobendan is absorbed best in an acidic environment. Fluctuating pH conditions in stomach and administration with food may produce inconsistent oral absorption.

In cats, pimobendan produces much higher blood concentrations than dogs and the half-life is almost three times longer than in dogs. Pimobendan is metabolized (demethylated) to desmethylpimobendan (DMP), which is an active metabolite with greater effect on PDE III activity. Both pimobendan and DMP are calcium sensitizers, but cats are less responsive to DMP than dogs.

Indications and clinical uses

Pimobendan is indicated for use in dogs for treatment of congestive heart failure (CHF). It has been used in dogs with either valvular insufficiency or cardiomyopathy. In dogs with heart failure caused by valvular disease, it decreased heart rate, decreased left ventricular and left atrial dimensions, and reduced preload and natriuretic peptide concentrations. It is considered by many cardiologists as an essential initial treatment for dilated cardiomyopathy in dogs. When used in dogs, it has improved signs of heart failure and increased survival. When used in dogs, it may be administered with diuretics (furosemide), spironolactone, and ACE inhibitors. Pimobendan treatment has produced significant improvement compared to placebo in dogs treated with an ACE inhibitor and a diuretic. Pimobendan also may be helpful for treating Doberman pinschers with occult (asymptomatic) dilated cardiomyopathy by prolonging onset of clinical signs, improving survival and overall outcome.

It has not been recommended to administer positive inotropic agents such as pimobendan to cats with hypertrophic cardiomyopathy. However, it has been associated with improvement in clinical signs and longer survival time in cats with heart failure associated with dilated cardiomyopathy as part of a therapeutic regimen that may include other drugs (e.g., furosemide). When administered at 1.25 mg/cat q12h (0.25 mg/kg), it has been well tolerated.

Precautionary information

Adverse reactions and side effects

Pimobendan is potentially arrhythmogenic, but this effect (e.g., atrial fibrillation or ventricular arrhythmias) has been rare and seen primarily in animals with severe underlying cardiac disease. At doses of 0.25-0.5 mg/kg in dogs, pimobendan did not activate the renin–angiotensin–aldosterone system (RAAS), but if furosemide is added to treatment, some activation of the RAAS may occur. At therapeutic doses, there has been negligible effect on platelet aggregation.

Contraindications and precautions

Use cautiously in animals prone to cardiac arrhythmias. Do not use in animals with obstructive cardiomyopathy or a fixed obstruction of the outflow tract. Compounded formulations will not achieve the same absorption profile in dogs as the proprietary form. There is a critical pH at which the oral absorption is enhanced, and some compounded formulations may lack excipients to attain this effect.

Drug interactions

Use cautiously with other PDE inhibitors such as theophylline, pentoxifylline, and sildenafil (Viagra) and related drugs. Sildenafil is a PDE V inhibitor; theophylline is a PDE IV inhibitor. 

Pimobendan is insoluble unless in an acidic environment, and it is difficult to mix pimobendan into a solution.

Instructions for use

Follow label instruction for use. Evaluate stage of heart failure in animals before use. Consider the addition of other drugs such as ACE inhibitors, spironolactone, furosemide, and digoxin in animals as the severity of the heart disease increases. If furosemide is used concurrently with pimobendan, consider the addition of an ACE inhibitor (e.g., enalapril, benazepril) or aldosterone antagonist (e.g., spironolactone) to inhibit RAAS activation.

Patient monitoring and laboratory tests

Monitor patient’s heart rate and rhythm during use.

Formulations

• Pimobendan is available in chewable tablets of 1.25, 2.5 and 5 mg. In Europe, pimobendan is available in 2.5- and 5-mg capsules.

Stability and storage

Store in a tightly sealed container, protected from light, and at room temperature. Acidic pH conditions are important for the stability of the formulation and to ensure dissolution.

Small animal dosage

Dogs

• 0.25-0.3 mg/kg q12h PO.

Cats

• 1.25 mg/cat q12h PO (0.1-0.3 mg/kg q12h).

Large animal dosage

• No doses have been reported for large animals.

Regulatory information

Do not administer to animals intended for food

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